title: A DNA element regulates drug tolerance and withdrawal in Drosophila.
abstract: Drug tolerance and withdrawal are insidious responses to drugs of abuse; the first increases drug consumption while the second punishes abstention. Drosophila generate functional tolerance to benzyl alcohol sedation by increasing neural expression of the slo BK-type Ca(2+) activated K(+) channel gene. After drug clearance this change produces a withdrawal phenotype-increased seizure susceptibility. The drug-induced histone modification profile identified the 6b element (60 nt) as a drug responsive element. Genomic deletion of 6b produces the allele, slo (Δ6b), that reacts more strongly to the drug with increased induction, a massive increase in the duration of tolerance, and an increase in the withdrawal phenotype yet does not alter other slo-dependent behaviors. The 6b element is a homeostatic regulator of BK channel gene expression and is the first cis-acting DNA element shown to specifically affect the duration of a drug action.
authors.affiliation: The Waggoner Center for Alcohol and Addiction Research, Section of Neurobiology, the University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Li
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ghezzi
authors.forename: Jascha B
authors.initials: JB
authors.lastname: Pohl
authors.forename: Arun Y
authors.initials: AY
authors.lastname: Bohm
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Atkinson
mesh_terms: D000483:Alleles; D000818:Animals; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics; D004361:Drug Tolerance / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels